Process for the preparation of organic cyclic carbonates and products prepared thereby



acid.

United States Patent Pennsylvania No Drawing. Filed May 31, 1963, Ser. N284,391

7 Claims. (Cl. 260-3402) This invention relates to a novel process forthe preparation of organic cyclic carbonates and to certain novelorganic cyclic carbonates prepared thereby.

Many 1,2-diols having pharmacodynamic activity such as muscle relaxant,tranquilizing, anti-convulsant and general central nervous systemdepressant activity are known to the art. By the process of thisinvention 1,2-diols are converted to organic cyclic carbonates whichhave generally the same kind of activity as the parent 1,2-diols.

The process of this invention comprises reacting a 1,2-diol compoundsuch as a vie-glycol or a benzene-o-diol with an excess of sodiumcyanate and an excess of triiluoroacetic acid to give organic cycliccarbonates. The diolcoznpound is preferably reacted with about 2-4 molarequivalents of sodium cyanate and about 2-4 molar equivalents oftrifiuoroacetic acid.

The reaction is carried out at temperatures of about 15-50 C. for areaction period of about 224 hours, preferably at about 30 C. for about-16 hours, in an inert organic solvent preferably a hydrocarbon such asbenzene or toluene, an ether such as diethyl ether or tetrahydrofuran ora halogenated hydrocarbon such as methylene chloride. The presence of asmall amount of Water in the reaction mixture is advantageous andresults in increased yields of the product.

The process of this invention is generally applicable to prepare organiccyclic carbonates from a wide variety of 1,2-diols. For example,according to the process of this invention organic cyclic carbonateshaving the formula:

(Formula I) when:

are prepared by reactinga 1,2-diol having the formula:

when R R R and R are as defined above with an excess of sodium cyanateand an excess of trifiuoroacetic When mercapto or additional hydroxygroups are present in the 1,2-diols said groups are converted tothiolcarbarnates and carbamates respectively under the above describedreaction conditions. Functional groups, such as olefins, ethers,sulfides and tertiary amines, which may be present in the 1,2-diols areunreactive in the process of this invention.

Patented Oct. 13, 1964 Further objects of this invention are novelorganic cyclic carbonates prepared by the process of this invention andrepresented by the following formula:

(Formula 11) R2 R2 R (B t) when R represents halogen having an atomicweight of less than or trifluoromethyl and R R and R represent loweralkyl.

These novel organic cyclic carbonates have pharmacodynamic activity, inparticular muscle relaxant, anticonvulsant and tranquilizing activity.

The following examples are not limiting but are illustrative of theprocess and compounds of this invention. Various changes andmodifications may be made in carrying out the process of this inventionWithout departing from the spirit and scope thereof. Insofar as thesechanges and modifications are within the purview of the appended claimsthey are considered as part of our invention.

Example 1 A mixture of 2.0 g. of Z-(p-chlorophenyl)-3-methyl-2,3-butanediol and 1.2 g. of sodium cyanate is treated with 2.06 g. oftrifluoroacetic acid and 75 ml. of ether. After 1.5 hours at roomtemperature, additional ether is added and the mixture is allowed tostand overnight at room temperature. The mixture is treated with water,neutralized with sodium bicarbonate and extracted with ether. The etherextracts are rinsed with 5% sodium bicarbonate solution and with waterand ether. After the ether extracts are dried, filtered and concentratedand the residue is chromatographed using benzene-tetrahydrofuran onneutral alumina, the product is2-(p-chlorophenyl)-3-methyl-2,3-butanediol cyclic carbonate, M.P. 77-80C.

Example 2 overnight and treated first with ml. of a saturated ammoniumchloride solution and then with 100 ml. of 2 N hydrochloric acid. Afterstirring for 30 minutes, the ethereal layer is separated andconcentrated in vacuo to give a solid which is recrystallized fromcyclohexane, a mixture of methanol-Water, and a mixture of cyclohexaneand benzene. White needles of 2-(p-triiluoromethylphenyl)-3-methyl-2,3-butanediol are obtained, M.P. 98 99 C.

'A solution of 3.75 g. of 2-(p-trifluoromethylphenyl)-3-methyl-2,3-butanedi0l in dichloromethane is treated with 1.95 g. ofsodium cyanate and 3.45 g. of trifluoroacetic acid. The resultingmixture is allowed to stand overnight at room temperature. The mixtureis washed with 20 ml. of water, dried, filtered and concentrated. Theresidue is dissolved in cyclohexane and benzene and filtered. Thefiltrate is chromatographed through neutral alumina in benzene to givethe cyclic carbonate of2-(p-trifluoromethylphenyl)-3-methyl-2,3-butanediol, M.P. 7l-74 C.

Example 3 A mixture of 2.6 g. of Z-(p-brornophenyl)-3-methyl-2,3-butanediol (prepared by the procedure of Example 3 2 usingl-bromo-4-iodobenzene as the starting material), 1.3 g. of sodiumcyanate and 2.4 g. of trifiuoroacetic acid in ether is allowed to standat 30 C. for 16 hours to give after Working up as in Example 1,Z-(p-bromophenyl)-3-methyi2,3-butanediol cyclic carbonate.

Similarly from 2-(o-chlorophenyl)-3-rnethyl-2,3-butanediol (prepared bythe procedure of Example 2 using l-chloro-Z-bromobenzene as the startingmaterial) the cyclic carbonate is prepared.

xample .4

By the procedure of Example 1 the following 1,2-diols are reacted atroom temperature with sodium cyanate and trifiuoroacetic acid in ether:

2- (rn-chlorophenyl) -3 methyl-2,3 -butanediol' 2- p-fiuorophenyl-3-methyl-2,3 -butanediol 2- (m-chlorophenyl)-3-rnethyl-2,3-pentanediolto give: 2-(rn-chlorophenyl)-3-methyl-2,S-butanediol cyclic car.-

bonate 2-(p-fiuorophenyl) -3-niethyl-2,3-butanediol cyclic carbonate andi 2-(m-chlorophenyl)-3-rnethyl-2,3-pentanediol cyclic carbonate,respectively.

Example 5 A mixture of 1.8 g. of B-(o-toloxy)-l,2-propauediol, 1.3 g. ofsodium cyanate and 2.3 g. of trilluoroacetic acid in ether is stirred atroom temperature for six hours. Working up as in Example 1 gives3-(o-toloxy)-1,2-propanediol cyclic carbonate. 5

Example 6 Two grams of 3-(o-rnethoxyphenoxy)-1,2-propanedio1, 1.5 g. ofsodium cyanate and 2.5 g. of trifiuoroacetic acid inSO ml. ofdichloromethane are mixed and the mixture is allowed to stand at roomtemperature for 16 hours to give, after working-up as in Example 1, thecyclic carbonate of 3-(o-methoxyphenoxy)-l,2-propanediol.

Example 7 A mixture of 16.6 g. of r-tertiary butylpyrocatechol, 13.0 g.of sodium cyanate and 22.8 g. of trifiuoroacetic acid in ether isallowed to stand at room temperature for 15 hours to give, after Workingup as in Example 1, the cyclic carbonate of 4-tertiary butylpyrocatechol.

Example 8 By the procedure of Example 2, Z-bromothiophene is treatedwith magnesium in ether and the resulting Grignard reagent is reactedwith TZ-methyl-Z-hydroxy-3-butanone to give3-methyl-2-(Z-thienyl)-2,3-butanediol.

A mixture of 9.3 g. of 3-methyl-2-(2-thienyl)-2,3-butanediol, 6.5 g. ofsodium cyanate and 11.4 g. of trifluoroacetic acid in 75 ml. of ether iskept at room temperature for 14 hours. Working up as in Example 1 gives3-methyl-2-(2-thienyl)-2,3-butanediol cyclic carbonate.

Example '9 By the procedure of Example 1, a mixture of 1.7 g. of2,3,6-trimethyl-2,3-heptanediol, 1.3 g. of sodium cyanate and 2.3 g. oftrifluoromethylacetic acid is allowed to stand 4 at 30 C. for 14 hoursto give, after Working up, the cyclic carbonate of2,3,6-trirnethyl-23-heptanediol.

What is claimed is: l. The process of preparing organic cycliccarbonates 5 which comprises reacting a member selected from the groupconsisting of a Vic-glycol and a benzene-o-diol with an excess of sodiumcyanate and an excess of tritluoroacetic acid.

2. The process according to claim 1 in which the reactron 15 carried outin an inert organic solvent.

3. The process according to claim 2 in which the reactron is carried outat 15-5 0 C.

4. The process of preparing organic cyclic carbonates having theformula: l5 1? 111 R1-o-- R in which:

R R R and R are members selected from the group consisting of hydrogen,lower alkyl, phenyl, benzyl,

phenethyl, phenoxymethyl and N-heterocyclic rings and, when takentogether with the carbon atoms to which they are attached, form anaromatic ring which comprises reacting a 1,2-diol having the formula: R2R3 Rho-oat;

OH OH in which R R R and R are as defined above with an excess of sodiumcyanate and an excess of trifiuoroacctic acid.

5 A compound having the formula:

'31 l a @e-r 40 R O\ /O I? 0 in which: R is a member selected from thegroup consisting of halogen having an atomic Weight of less than 80 andrifluoromethyl and R R and R are lower alkyl. 6. A compound having theformula: (RH3 (3H3 I O 7. A compound having the formula:

CH3 CH3 Cl CH l 1 a O\ /O C n O No references cited.

1. THE PROCESS OF PREPARING ORGANIC CYCLIC CARBONATES WHICH COMPRISESREACTING A MEMBER SELECTED FROM THE GROUP CONSISTING OF A VIC-GLYCOL ANDA BENZENE-O-DIOL WITH AN EXCESS OF SODIUM CYANATE AND AN EXCESS OFTRIFLUOROACETIC ACID.
 5. A COMPOUND HAVING THE FORMULA: